Naturally occurring deletions/insertions in HBV core promoter tend to decrease in HBeAg-positive chronic hepatitis B patients during antiviral therapy.

Antiviral therapy

PubMedID: 25838313

Peng Y, Liu B, Hou J, Sun J, Hao R, Xiang K, Yan L, Zhang J, Zhuang H, Li T. Naturally occurring deletions/insertions in HBV core promoter tend to decrease in HBeAg-positive chronic hepatitis B patients during antiviral therapy. Antivir Ther (Lond). 2015;.
BACKGROUND
Mutations in HBV core promoter (CP) are suggested to affect viral replication and disease progression. We investigated CP deletion/insertion mutations (Del/Ins) in HBeAg-positive chronic hepatitis B (CHB) patients before and during antiviral treatment.

METHODS
Direct and clone sequencings were used for detection of CP Del/Ins in 12 patients. The dynamic changes of CP Del/Ins were tracked in these cases until week 48 of treatment. The effects of Del/Ins on CP activities and HBx were analyzed using luciferase assay and sequence comparison, respectively. Furthermore, 292 untreated HBeAg-positive CHB cases were also analyzed.

RESULTS
Twelve cases with multi-peak PCR direct sequencing electropherograms at baseline were confirmed to have CP Del/Ins by clone sequencing, with detection rates varying from 14.8% to 93.3% of clones analyzed. Follow-up studies showed the detection rates of CP Del/Ins in patients decreased from 100% (12/12) at baseline to 16.7% (2/12) at week 48 of treatment (P < 0.001), in parallel with a decline in HBV DNA, HBsAg, ALT and AST levels along with an increase in HBeAg loss. Luciferase assay results showed distinct promoter activities among Del/Ins-harboring CP sequences. Importantly, 71.8% (148/206) of Del/Ins sequences potentially resulted in HBx carboxy-terminal truncations. CP Del/Ins mutations were also found in 27.4% (80/292) of untreated cases.

CONCLUSIONS
Naturally occurring complex of CP Del/Ins mutants existed in untreated HBeAg-positive CHB patients. These mutations would affect HBV transcription activities and integrity of HBx, which might correlate with disease progression. Their prevalence decreases on antiviral therapy in parallel with the decline in HBV DNA, HBsAg and ALT and AST levels.